Following a request on Twitter, this post summarises some of the major research developments in dementia science between the time when my book The Fragile Brain was submitted (March 2016) and its publication last month (November 2016).

Treatments

The big clinical news is surely the failure of the solanezumab trial, based on the amyloid cascade hypothesis. Some researchers reacted by giving reasons why the failure didn’t kill the hypothesis; others remarked that you can’t kill something that’s already dead. Apart from its implications for research, this is another setback for patients desperate for good news.

Lifestyle

Good news may yet arrive from treatment trials, but we got some by another route this year, courtesy of big epidemiological studies such as Langa et al. and Matthews et al.. These support the idea that dementia rates may be slowing, at least in Western countries like the UK. That suggests that the lifestyle changes people have made so far may be having an effect.

These changes are sizeable. In the UK, for instance, smoking has dropped from 46% to 19% of adults since 1974, according to the Office for National Statistics. If so much change is possible, perhaps there’s hope for other risk factors like overeating, pollution, and physical inactivity. It would help if governments would take them more seriously, though there are hints of progress here too, such as the new UK sugar tax. Countries in which smoking rates remain high and diets are becoming more Western are storing up trouble – and expense – for future generations.

Research

In research, one obvious change (certainly since I began work on The Fragile Brain) is that neuroimmunology – and the broader acceptance that blood factors can and do affect the brain far more than previously thought – is now mainstream. For example, the journal Neuropsychopharmacology has just issued a table of contents on the topic (Volume 42, Issue 1, January 2017). Emphasis on diabetes and depression as risk factors has increased accordingly, given the importance of inflammation in these disorders. Research into the gut and microbiome, and their potential impact on ageing brains, is also gathering pace (e.g. Sampson et al.).

Complementing this is the growing understanding that the brain’s non-neuronal cells – such as astrocytes, microglia, oligodendrocytes, pericytes and endothelial cells – really matter for neurons’ and synapses’ wellbeing. These formerly neglected cells, and the vascular system, are vital for keeping the brain healthy into old age (see e.g. Ma et al.).

Efforts continue to make the impact of new methods, such as organoids, ‘omics’ and neuroimaging, felt in neurodegeneration research, and to organise the masses of data they produce (see e.g. Rollo et al.). It’s becoming clearer that lipids, and the cell membrane, are more important players than previously realised, which potentially opens up new treatment and dietary avenues for research. For proteins, the importance of variants in genes other than ApoE, such as TREM2, is becoming more apparent, and ApoE studies are also branching out.

This is a brief summary of recent developments; there’s much more than I’ve covered here. It’s a fast-moving field, and 2017 should bring plenty of advances in basic research. And treatments? Well, here’s hoping. Perhaps some of the other antibody trials, or alternative approaches such as insulin, will produce encouraging results.

Whatever happens in 2017, in dementia research and elsewhere, I wish you a successful new year.

Images, like the view of the thalamus shown here, look great, but they need words, or a lot of background knowledge, to communicate their meaning.

So it’s back to words. But what kind of words? Well, it’s said that fiction’s a good way of communicating … in some cases anyway!

I’m not too keen on the idea that science is science and should steer well clear of anything that smacks of the humanities. People have quite enough tricks for emphasizing their differences, and feeling superior in consequence, without barricading intellectual endeavours into disciplinary silos. (I know, I know, talk about championing a lost cause!) Besides, neuroscientists are happy to use the visual arts to put their work across, so why not other art forms?

All fiction is in a sense concerned with brains’ activities, but not many authors have tried writing fiction about brains themselves. Pondering this one day, I thought: “Someone should write a short story about brains! I’d read it! Probably.” Then I went back to reading whatever exciting science article had just fallen out of my inbox and onto my to-do list.

Some time later this short story wandered into my brain. It made me smile, so I caught the thing and submitted it to a writing competition (Writers and Artists) on the theme of ‘freedom’, where, to my astonishment, it was short-listed. You can download it as a PDF here (‘Freedom’, by Neurotaylor). I’m posting it on this blog as an exercise in alternative methods of science communication.

And If you know of any great fiction about brains themselves, let me know.

Here’s the story, set out as a taster so the post isn’t too long. The whole thing’s around 2000 words.

Freedom

Alright mate? You on the tour? Welcome to the department. I’m Alfie.

Ever been inside a brain before? No? That’s unusual, not many people start their visit here.

Fully booked, eh? Don’t apologise, mate, we’re used to it. People wanna see the bits they’ve heard of. It’s all, “Ooh, can we go to the prefrontal cortex?”, like that’s the only department that matters. I tell you, mate, without us those guys in prefrontal would be twiddling their dendrites and rotting.

Yeah, they don’t half play up to it though. You’ll see ’em later. All that, “Oh yes, it’s a great responsibility”, and banging on about their dopamine levels, as if the rest of us never get a sniff of dopamine. They don’t half try it on, that lot. They’re just passing messages, same as the rest of us.

‘Mind control? I wish!’ is an understandable response, but is mocking humour the best response to anxiety? That’s a serious question, and the answer depends on the humourist’s goal. Is it to preserve status and protect neuroscience’s reputation, or is it to ease the concerns of people who take the prospect of imminent brainwashing seriously? The media do sensationalise, but they don’t do so at random; they generally know what works. People fear being manipulated.

Of course some researchers will react dismissively. Who wants their shiny new science tainted by association with the sordid cruelties of early brainwashing research? But before you dismiss the idea, bear in mind that the leading scientists behind the Brain Activity Mapping Project, which US President Obama hopes to back with $3 billion funding, raise the issue of mind control themselves as one of the difficult ethical problems which may arise in the course of their research (their article in Neuron is here).

The Frankenstein stereotype of scientists as seeking to dominate nature remains influential, and in brain research, of course, ‘nature’ means ‘us’. If you don’t know the gritty details which make neuroscience research so painstaking and difficult, it’s easy to imagine the worst.

And the pressure on scientists to hype up the ‘impact’ of their work, stretching steps to advances, advances to breakthroughs, and breakthroughs to exciting challenges, is not helpful either. If one neuroscientist’s press release says he’s used fMRI to decode what somebody’s thinking, is it quite fair for another’s blog to sneer at those poor fools who fear that the government may soon be reading their minds?

To be clear: the issue of mind control may arise. No way can we do it yet, and no researcher knows whether it will be possible or not in the future. The brain’s really hard, but science is littered with people who said ‘never’ and were proved wrong, so the opinions for and against are matters of personality and faith, not secret knowledge. Cynics will sneer, optimists hope, pessimists dread, psychopaths plot, and geeks plough on regardless — and entertaining though this all may be, it’s not science.

Meanwhile, there’s more danger of mind control from watching TV ads too long than from your local neuroscience lab. Even if precision brain control does become a real possibility, my own expression of faith is that you probably have more to fear from your (nonlocal) megacorporations, government and the military than your friendly neighbourhood brain researchers.

Having written books about both brainwashing and the future of neuroscience technologies, I herewith add my tuppenceworth on why we find the topic so enthralling, in the form of a short video about the ancient dream, and modern science, of mind control.

(Apologies for the fit of the giggles that overtook my interviewer, and then me, in the MEG video, requiring some urgent, but rather amateur, editing.)

My hope is that these guides will be useful to students starting out, and to anyone who wants a quick briefing on what happens in brain scans. I’ve tried to keep the talks short, clear, and as fluent as possible. I’ve put slides in at intervals to help summarise the material, and there are some questions at the end for those who’d like pointers to further study.

It tests what you type in the box (in English) against a list of the most commonly-used words. The ‘ten hundred’ most common — presumably described that way because ‘thousand’ isn’t a common enough word.

Now, I’m not altogether in favour of this. What’s the point of having all those gorgeous words to play with if you don’t use them and, by using them, encourage other people to use them too? The connection between language and thought is, shall we say, contested — philosophers have been arguing over it for ages and show no signs of desisting any time soon — but I’m tempted by George Orwell’s 1984 view here: simplify and restrict language, and you risk restricting the minds that express themselves through it.

On the other hand, I am in favour of clarity, and using language carefully. And it’s a fun challenge.

The brain is a very hard thing to understand. It’s full of very many bits and pieces, such as cells and the things inside them, which talk to each other in very many ways. That makes for a problem: how do we get a grip on all those conversations inside the cells and between cells? Understanding has to be done bit by bit, and there are lots and lots of bits. Too many for any one person to get their head around. Together, those bits make up us. They allow us to think, feel, act, believe and be the amazing humans we are.

Like this:

Today I’m trying a new experiment. New for me, at least, and scary, though no doubt many of you will be past masters at it. I’m posting a video on YouTube. It’s the first of a planned series of short, simple talks about neuroscience, and it’s an introductory guide to what’s where in human brains.

My hope is that it will be useful to students starting out, and to others interested in learning more about brains and the methods used to study them. If you’d like to look a little beyond the headlines and pretty pictures of fMRI, for instance, there’ll be a talk on that coming soon.

I’ve tried to keep the talks short, clear, and as fluent as possible, although, as I soon found out, it’s extremely difficult to talk coherently for minutes at a time about any subject, even one you know well.

Finally, the biggest disadvantage to this project, from my point of view, is that it’s video. My childish sympathy for the old idea that photographing someone stole their soul has been overlaid in adulthood by a properly scientific doubt as to whether people have souls – but I retain the child’s dislike of being imaged. However, communication works better when you can see the communicator. And this is such an important topic to communicate. So here goes.

Like this:

Years ago now, I recall a senior scientist who’d read a piece of my work saying doubtfully, ‘It’s very well-written. Very literary.’ The implication was clear: ‘But is it good science?’

With hindsight, I can agree: that particular effort wasn’t ace. I can’t even remember its title, and the obscurity’s well-deserved. What did stick was my surprise that my colleague (undoubtedly a good scientist) saw good science and good writing as not just independent, but even perhaps opposed, since science is all about precision and language is irretrievably vague.

I’m a science writer. I signed up long ago to the principles of open science, and I do my best to let people know about the magnificent achievements of modern neuroscience. Insofar as introverts can be evangelical, I’m spreading the good news about brain research. To do this, I and many others like me need publicity. We need the media.

And yet, I have a deep and growing fear that the current excited courtship between research, especially brain research, and the media may not necessarily be the good thing people seem to think it is.

This is not just the usual anxiety about requirements for ‘impact’ in funding applications, and the distorting effects of rewarding instantly popular research (see for instance this report from NHS Behind the Headlines). It’s more fundamental, and it’s particularly relevant to the sciences of the mind and brain.

A fascinating paper in the journal PNAS, this. OK, it’s in patients (pretty much has to be, given they’re using intracranial electrodes), and only three of them, but it offers tantalising ground for speculation, which is always fun. And it shows how influential the notion of brain oscillations is becoming. ‘Tweren’t always thus.

Behaviour: epilepsy patients were tested during loss of consciousness by being given the anaesthetic propofol and asked to press a button when they heard a (frequent) tone. Two consecutive non-responses were taken to mean that the anaesthetic had successfully knocked them out. Propofol boosts GABAergic activity.

Brain recordings: these were taken of the intracranial electrocorticogram (i.e. global electrical activity, if one can call the brain a globe), single neurons, and the intermediate level of the local field potential (LFP), all in the same region, temporal cortex. Nice.

Findings: what the authors found, in their own words, was ‘a functional isolation of cortical regions while significant connectivity is preserved within local networks’, slow oscillations in the local field potential, and ‘short periods of normal spike dynamics still can occur during unconsciousness’. Initially neuronal spiking is suppressed, but though cells’ activity may recover to pre-anaesthetic levels, the patterns are different — short bursts, interspersed with silence, the activity coupled to the slow oscillations. And the patient remains unconscious.

Conclusions: so to put it crudely, consciousness doesn’t seem to depend on the number of spikes, so much as on the long-range connections between active areas. The local slow oscillations, which look a bit like the slow waves of slow-wave sleep (but more fragmented and with faster onset), appear to have different phases in different areas, suggesting that coupling between areas is interrupted. Apologies if this is starting to sound like a bad neuro take-off of Fifty Shades of Grey, but in consciousness, it seems, coupling’s what it’s all about.

Having said which, as the authors point out, they don’t yet know ‘whether the slow oscillation is sufficient to produce unconsciousness’. And this kind of functional breaking up may not be the only way in which we humans can be rendered temporarily insensate. MRN, of course (more research needed).

Still, it’s interesting to think about implications: for attempts to create artificial conscious entities, for what may be going on in Alzheimer’s, and for the science of dreams, to name but three. All those patients’ reports of strange sensations and half-remembered awareness while supposedly unconscious seem less neurotic now. Fascinating stuff!

Like this:

The brain supremacy is a great, rapidly-developing change in science, in which the traditional dominance of the physical sciences will be challenged, and then usurped, by the growth of the biological, and especially the brain sciences.

When that happens, our culture, including the culture of science, will have to change, because both are built on outdated assumptions. As a bonus, the change could take scientific hubris down a peg or two, as we realise just how much harder brains are to study than anything we’ve tackled so far. That’s no harm either! Humility’s an unfashionable virtue in this self-promoting age, and it’s a lot harder to slip from confidence to arrogance when you’re trying to analyse a living brain.

Three great flows in the river of science are converging. Expect a white-water ride, as the power of physics-derived brain research methods and the force of the genetics revolution meet the youthful energy of a science emerging from childhood into a fully-fledged research field. When I started out, neuroscience was a branch of physiology. No longer.

The brain supremacy can’t come soon enough for me, for three reasons. Firstly, because time’s getting on in this particular life-path! Secondly, because it’s going to be amazing to watch. Neurotech is already phenomenal; as the brain supremacy takes shape its power will reach awe-inspiring capacities. How about dream recording, selective memory erasure, mindreading? How about the facility to share dreams, or download artificial experiences? How about the ability to reprogramme your beliefs and desires? It’s going to be a fascinating journey, seeing even a few of these promises come to pass.

Finally, thirdly, there’s my great hope: that the brain supremacy could make us all more human. Minds need more careful handling than rocks or proteins; the ethical constraints are tighter. The potential for misuse of the new technologies — which is admittedly nightmarish — will, I hope, make us more careful of each other. Every human brain is gloriously unique. The more we recognise that, the harder it may become to commit the atrocities which ruin and destroy them …

… and the easier it will get to work towards cures for hurt neurons. Think what we could do if we gained the gift of precision brain control. Might fanaticism, violence and psychopathy become curable disorders? Might the hideous damage inflicted by childhood abuse, or the diseases of old age, be reversible at last? Those are goals worth chasing.

I’m so lucky to be alive to see this time when, more than ever before, we hold the hope of a better future in our hands.